Transport mechanisms at the blood-brain barrier were studied in the rat. An in vivo brain perfusion technique was developed to examine carrier-mediated transport at the cerebral capillary endothelium. Brain perfusion with Ringer's solution or with blood did not alter cerebrovascular permeability to sucrose. Barrier permeability to nonelectrolytes was linearly related to lipid solubility. Large neutral amino acids cross the blood-brain barrier by facilitated diffusion. The cerebrovascular permeability to inorganic ions was low, comparable to a cell membrane, and followed the sequence K greater than Mg greater than Na greater than Cl greater than Ca. Chloride transport across the blood-brain barrier was by a saturable, carrier-mediated system, which was inhibited by other monovalent anions. The low permeability of the cerebrovascular endothelium to Na was maintained with age in the rate, whereas the cerebrospinal fluid transfer constant for Na fell by 18%.